A new spectroscopic technique, rotational-echo double-resonance (REDOR) NMR, for solids utilizes magic-angle spinning and measures directly the dipolar coupling between stable-isotope-labeled nuclei ...and, thus, interatomic distances. REDOR has been used to measure the {sup 13}C-{sup 15}N interatomic distance in a nine-residue fragment, Ac-Phe-MeA(1-{sup 13}C)-MeA(d{sub 6})-MeA-Val-Gly({sup 15}N)-Leu-MeA-MeA-OBzl (MeA = {alpha}-methylalanine or aminoisobutyric acid (Aib)), of the peptide antibiotic emerimicin. The crystal structure of the peptide emerimicin 1-9 benzyl ester was determined previously, and the measurement by REDOR of a known interatomic distance allows both validation and a practical demonstration of the precision of REDOR. The ability to map precisely intermolecular distances suggests applications of REDOR in the solid, or aggregated state, for determinations of the conformations of ligand molecules in drug-receptor, inhibitor-enzyme, and antigen-antibody complexes.
The fully blocked pentapeptide Tfa-(Deg)2-L-Abu-(Deg)2-OtBu (Tfa: triflouroacetyl; Deg: C alpha, alpha-diethylglycine; Otbu: tert-butoxy) adopts in the crystal state a regular, right-handed ...3(10)-helical structure stabilized by three N--H...O=C intramolecular 1 < 4 (or C10) H bonds, as determined by an x-ray diffraction analysis. However, a Fourier transform ir absorption and 1H-nmr study strongly supports the view that in deuterochloroform solution the four Deg residues at both termini of the peptide main chain are involved in successive, fully extended C5 forms. A comparison with the stable, fully developed, multiple C5 conformation of Tfa-(Deg)5-OtBu indicates that incorporation of an Abu guest residue, interrupting the side-chain uniformity of the host (Deg)5 homopeptide, while altering only marginally the conformation in a solvent of low polarity, is responsible for a dramatic perturbation of the crystal-state structure.
2-Phenyl-4-alkyl-4-hydroxymethyl-1,3-oxazolones (2a-d) have been identified as side products accompanying activation of N-benzoyl-2-alkylserines (1a-d). Oxazolones 2a-d in the presence of amine ...rearrange subsequently to corresponding 4-alkyl-2-phenyl-4,5-dihydro-1,3-oxazole-5 carboxylic acids (4a-d) at a 20-68% yield.
The syntheses and the crystal structures of the C-terminal tetrapeptide fragments of emerimicin IV and III, Boc-R-EtA-Hyp(Bzl)-Ala-Phol and Boc-R-EtA-Hyp(Bzl)-MeA-Phol, containing the chiral ...alpha,alpha-dialkyl amino acid, R-alpha-ethylalanine (R-EtA) are reported. The two peptides are isomorphous and assume a 3(10)-helical conformation in the crystal. A comparison of the crystal data on alpha,alpha-dialkyl amino acids indicates that alkyl substituents larger than a methyl group do not preclude peptides containing these amino acids from assuming the conformations associated with minima which have been well characterized for alpha-methylalanine.
A new synthetic protocol which considerably improves the classic REMA procedure is proposed herein. The offered modification is based on the application of triazine "superactive esters" as the ...superior substitutes for mixed anhydrides, which have been used as acylating reagent in the classic procedure. The improved repetitive procedure in solution was applied to the preparation of 54-59 fragment of human beta-casein. The structure and high purity of the intermediates, as well as of the final products, was confirmed by FAB-MS, 1H-NMR and HPLC.
N-terminal fragment of emerimicin III has been synthesized by the repetitive method in solution, involving triazine ,,superactive esters". The synthetic protocol, equivalent to the classic REMA ...procedure, has been applied in the step by step approach, and in the fragment coupling affording all the peptide bonds. By monitoring the progress of the synthesis by FAB-MS, 1H-NMR and HPLC, the structure and high purity of the final products have been confirmed.
The compound CH
-CO-NH-C(C
-COOH was synthesized from the corresponding free amino acid. N-Acetyl-C
-diethylglycine crystallizes in the monoclinic space group P2
/c with a = 13.551(2)Å, b = ...11.110(3)Å, c = 13.569(3)Å, β = 111.54(2)°, Z = 8 , D = 1.21 g/cm
. This structure was solved by direct methods and refined to R = 0.084. N-Acetyl-C
-diethylglycine shows a fully extended conformation in its -N H-C(C
-CO- part.
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